Éditeur(s) : Université des Antilles AREBio Groupe de recherche BIOSPHERES : BIOlogie, Sciences Physiques & Humaines pour les énergies Renouvelables, l
Extrait de : 1er colloque international BIOSPHERES, du 18 au 20 juin 2019. Université des Antilles
Description : Drosophila often offers many advantages as an experimental organism. The dead ringer (dri) gene of drosophila melanogaster is a member of the recently discovered ARID-box family of eukaryotic genes that encodes proteins with a conserved DNA-binding domain. dri itself is highly well conserved with specific orthologs from human to yeast genomes. This family include ARID3A, 3B and 3C with have role in embryonic pattening, cell lineage gene regulation, cell cycle control, transcriptional regulation and chromatin structure modification. We first showed that the gene encoding ARID3A also known as Bright (B cell regulator of immunoglobulin heavy chain transcription) play critical roles in B-cell development and SATB1 in T-cell transcription regulation. In this international workshops we will expose a comprehensive understanding of these molecules and better knowledge of their specific targets and function-interactions in controlling cell fate decisions and development. In addition, dri have homology with the Aedes aegypti mosquitoes which had ability to carry and spread disease to human. More than half of the world?s population live in areas where this mosquito species is present, including Martinique. Sustained mosquito control efforts are important to prevent outbreaks from Dengue, Chikungunya, malaria, zika diseases. Discovering the functions of AT-rich genes in preventing illness from mosquito is the central goal for raising working progress hypothesis.

Droits : CC-BY-NC-ND - Attribution - Pas d'utilisation commerciale - Pas de modification
Permalien : http://www.manioc.org/fichiers/V19077
V19077

Éditeur(s) : HAL CCSD Endocrine Society
Résumé : International audience
Transcriptional regulation by the estrogen receptor-alpha(ER) has been investigated mainly in breast cancer cell lines, but estrogens such as 17 beta-estradiol (E2) exert numerous extrareproductive effects, particularly in the liver, where E2 exhibits both protective metabolic and deleterious thrombotic actions. To analyze the direct and early transcriptional effects of estrogens in the liver, we determined the E2-sensitive transcriptome and ER cistrome in mice after acute administration of E2 or placebo. These analyses revealed the early induction of genes involved in lipid metabolism, which fits with the crucial role of ER in the prevention of liver steatosis. Characterization of the chromatin state of ER binding sites (BSs) in mice expressing or not ER demonstrated that ER is not required per se for the establishment and/or maintenance of chromatin modifications at the majority of its BSs. This is presumably a consequence of a strong overlap between ER and hepatocyte nuclear factor 4 alpha BSs. In contrast, 40% of the BSs of the pioneer factor forkhead box protein a (Foxa2) were dependent upon ER expression, and ER expression also affected the distribution of nucleosomes harboring dimethylated lysine 4 of Histone H3 around Foxa2 BSs. We finally show that, in addition to a network of liver-specific transcription factors including CCAAT/enhancer-binding protein and hepatocyte nuclear factor 4 alpha, ER might be required for proper Foxa2 function in this tissue.
ISSN: 0888-8809

hal-01357623
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01357623/file/Changes%20in%20gene%20expression%201%20and%20Estrogen%20Receptor_accepted.pdf
DOI : 10.1210/me.2015-1311

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
A hallmark of living systems is the management and the storage of information through genetic and epigenetic mechanisms. Although the notion of epigenetics was originally given to any regulation beyond DNA sequence, it has often been restricted to chromatin modifications, supposed to behave as cis-markers, specifying the sets of genes to be expressed or repressed. This definition does not take into account the initial view of epigenetics, based on nonlinear interaction networks whose "attractors" can remain stable without need for any chromatin mark. In addition, most chromatin modifications are the steady state resultants of highly dynamic modification and de-modification activities and, as such, seem poorly appropriate to work as long-term memory keepers. Instead, the basic support of epigenetic memory could remain the attractors, to which chromatin modifications belong as do many other components. The influence of chromatin modifications in memory is highly questionable when envisioned as static structural marks, but can be recovered under the dynamic circuitry perspective, thanks to their self-templating properties. Beside their standard repressive or permissive functions, chromatin modifications can also influence transcription in multiple ways such as: (1) by randomizing or inversely stabilizing gene expression, (2) by mediating cooperativity between pioneer and secondary transcription factors, and (3) in the hysteresis and the ultrasensitivity of gene expression switches, allowing the cells to take unambiguous transcriptional decisions.
ISSN: 1420-682X

hal-01063617
https://hal.archives-ouvertes.fr/hal-01063617
DOI : 10.1007/s00018-012-0923-7
PUBMED : 22331281

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
High-mobility group box-1 (HMGB1) is remarkably mobile in living cells, which reflects its ability to interact only transiently with both DNA and protein. This property is likely essential for HMGB1 nuclear activities. Nonetheless the weak interaction of HMGB1 with DNA and/or protein partners has also been a major limitation for investigating HMGB1 subnuclear localisation and for the identification of HMGB1 containing complexes by conventional biochemical approaches. In the present study, FRAP experiments demonstrated that DsRed-mediated oligomerization strongly reduces HMGB1 mobility due to an increased affinity for cellular chromatin. Moreover, oligomerized DsRed HMGB1 exhibited a higher affinity for supercoiled DNA in vitro compared to its monomeric counterpart. These results indicate that DsRed-meditated oligomerization is prone to stabilize labile interactions involving HMGB1 both in vivo and in vitro.
ISSN: 0300-9084

hal-01546170
https://hal.archives-ouvertes.fr/hal-01546170
DOI : 10.1016/j.biochi.2012.11.001

Éditeur(s) : HAL CCSD
Résumé : International audience
In addition to soluble factors, mechanical constraints and extracellular matrix stiffness are important regulators of cell fate that are mediated by cytoskeletal modifications. The EMT (epithelial-mesenchymal transition) that occurs during normal development and malignant progression is a typical example of the phenotypic switch associated with profound actin remodelling and changes in gene expression. For instance, actin dynamics control motile cell functions in EMT, in part, through regulating the subcellular localization of the myocardin-related transcription factor MKL1 (megakaryoblastic leukaemia translocation 1), a co-activator of SRF (serum-responsive factor). In the present paper, we show that MKL1 participates also to the control of the cellular switch between growth and quiescence. Experimental disconnection between MKL1 and G-actin (globular actin), by using an MKL1 mutant or enhancing the F (filamentous)-/G-actin ratio, generates a widely open chromatin state and a global increase in biosynthetic activity, classically associated with cell growth. Conversely, G-actin accumulation favours nuclear condensation and cell quiescence. These large-scale chromatin changes rely upon extensive histone modifications, exemplified by that of H3K9 (H3 Lys9) shifting from trimethylation, a heterochromatin mark, to acetylation, a mark of euchromatin. The present study provides the first evidence for a global reversible hetero/euchromatinization phenomenon triggered by the actin/MKL1 signalling pathway.
The Biochemical Journal

hal-01063933
https://hal.archives-ouvertes.fr/hal-01063933
DOI : 10.1042/BJ20131240
PUBMED : 24762104

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Chromatin modification enzymes are important regulators of gene expression and some are evolutionarily conserved from yeast to human. Saccharomyces cerevisiae is a major model organism for genome-wide studies that aim at the identification of target genes under the control of conserved epigenetic regulators. Ume6 interacts with the upstream repressor site 1 (URS1) and represses transcription by recruiting both the conserved histone deacetylase Rpd3 (through the co-repressor Sin3) and the chromatin-remodeling factor Isw2. Cells lacking Ume6 are defective in growth, stress response, and meiotic development. RNA profiling studies and in vivo protein-DNA binding assays identified mRNAs or transcript isoforms that are directly repressed by Ume6 in mitosis. However, a comprehensive understanding of the transcriptional alterations, which underlie the complex ume6Δ mutant phenotype during fermentation, respiration, or sporulation, is lacking. We report the protein-coding transcriptome of a diploid MAT a/α wild-type and ume6/ume6 mutant strains cultured in rich media with glucose or acetate as a carbon source, or sporulation-inducing medium. We distinguished direct from indirect effects on mRNA levels by combining GeneChip data with URS1 motif predictions and published high-throughput in vivo Ume6-DNA binding data. To gain insight into the molecular interactions between successive waves of Ume6-dependent meiotic genes, we integrated expression data with information on protein networks. Our work identifies novel Ume6 repressed genes during growth and development and reveals a strong effect of the carbon source on the derepression pattern of transcripts in growing and developmentally arrested ume6/ume6 mutant cells. Since yeast is a useful model organism for chromatin-mediated effects on gene expression, our results provide a rich source for further genetic and molecular biological work on the regulation of cell growth and cell differentiation in eukaryotes.
ISSN: 1617-4615

hal-01151619
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01151619
DOI : 10.1007/s00438-015-1051-5
PUBMED : 25957495

Éditeur(s) : HAL CCSD Elsevier
Résumé : This manuscript is an extended version, including an updated bibliography, of the article: Hierarchical cooperativity mediated by chromatin remodeling; the model of the MMTV transcription regulation. Michel, D. 2011. J. Theor. Biol. 287, 74-81
International audience
Chromatin remodeling machineries are abundant and diverse in eukaryotic cells. They have been involved in a variety of situations such as histone exchange and DNA repair, but their importance in gene expression remains unclear. Although the influence of nucleosome position on the regulation of gene expression is generally envisioned under the quasi-equilibrium perspective, it is proposed that given the ATP-dependence of chro-matin remodeling enzymes, certain mechanisms necessitate non-equilibrium treatments. Examination of the celebrated chromatin remodeling system of the mouse mammary tumor virus, in which the binding of transcription factors opens the way to other ones, reveals that breaking equilibrium offers a subtle mode of transcription factor cooperativity, avoids molecular trapping phenomena and allows to reconcile previously conflicting experimental data. This mechanism provides a control lever of promoter responsiveness to transcription factor combinations, challenging the classical view of the unilateral influence of pioneer on secondary transcription factors.
ISSN: 0022-5193

hal-01211233
https://hal.archives-ouvertes.fr/hal-01211233
https://hal.archives-ouvertes.fr/hal-01211233/document
https://hal.archives-ouvertes.fr/hal-01211233/file/nucleosome.pdf
ARXIV : 1509.07440

Éditeur(s) : HAL CCSD
Résumé : International audience
The epigenetic mark 5-hydroxymethylcytosine (5hmC) is a cytosine modification that is abundant in the central nervous system of mammals and which results from 5-methylcytosine oxidation by TET enzymes. Such a mark is suggested to play key roles in the regulation of chromatin structure and gene expression. However, its precise functions still remain poorly understood and information about its distribution in non-mammalian species is still lacking. Here, the distribution of 5hmC was investigated in the brain of adult zebrafish, African claw frog, and mouse in a comparative manner. We show that zebrafish neurons are endowed with high levels of 5hmC, whereas quiescent or proliferative neural progenitors show low to undetectable levels of the modified cytosine. In the brain of larval and juvenile Xenopus, 5hmC is also detected in neurons, while ventricular proliferative cells do not display this epigenetic mark. Similarly, 5hmC is enriched in neurons compared to neural progenitors of the ventricular zone in the mouse developing cortex. Interestingly, 5hmC colocalized with the methylated DNA binding protein MeCP2 and with the active chromatin histone modification H3K4me2 in mouse neurons. Taken together, our results show an evolutionarily conserved cerebral distribution of 5hmC between fish and tetrapods and reinforce the idea that 5hmC fulfills major functions in the control of chromatin activity in vertebrate neurons. J. Comp. Neurol. 525:478-497, 2017. © 2016 Wiley Periodicals, Inc.
Journal of Comparative Neurology

hal-01439354
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01439354
DOI : 10.1002/cne.24077
PUBMED : 27414756

Éditeur(s) : HAL CCSD Cold Spring Harbor Laboratory Press
Résumé : “Human and Environmental Genomics” platform (Rennes) for Illumina sequencing / Proteomics Core Facility of the Cambridge Institute (Cancer Research UK)
International audience
Epigenetic mechanisms are believed to play key roles in the establishment of cell-specific transcription programs. Accordingly, the modified bases 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been observed in DNA of genomic regulatory regions such as enhancers, and oxidation of 5mC into 5hmC by Ten-eleven translocation (TET) proteins correlates with enhancer activation. However, the functional relationship between cytosine modifications and the chromatin architecture of enhancers remains elusive. To gain insights into their function, 5mC and 5hmC levels were perturbed by inhibiting DNA methyltransferases and TETs during differentiation of mouse embryonal carcinoma cells into neural progenitors, and chromatin characteristics of enhancers bound by the pioneer transcription factors FOXA1, MEIS1, and PBX1 were interrogated. In a large fraction of the tested enhancers, inhibition of DNA methylation was associated with a significant increase in monomethylation of H3K4, a characteristic mark of enhancer priming. In addition, at some specific enhancers, 5mC oxidation by TETs facilitated chromatin opening, a process that may stabilize MEIS1 binding to these genomic regions.
ISSN: 1088-9051

Droits : http://creativecommons.org/licenses/by-nc/
hal-01533248
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01533248
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01533248/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01533248/file/Genome%20Res.-2017-Mah%C3%A9-947-58.pdf
DOI : 10.1101/gr.211466.116

Éditeur(s) : HAL CCSD
Résumé : International audience
Despite their dynamic nature, certain chromatin marks must be maintained over the long term. This is particulary true for histone 3 lysine 9 (H3K9) trimethylation, that is involved in the maintenance of healthy differentiated cellular states by preventing inappropriate gene expression, and has been recently identified as the most efficient barrier to cellular reprogramming in nuclear transfer experiments. We propose that the capacity of the enzymes SUV39H1/2 to rebind to a minor fraction of their products, either directly or via HP1α/β, contributes to the solidity of this mark through (i) a positive feedback involved in its establishment by the mutual enforcement of H3K9me3 and SUV39H1/2 and then (ii) a negative feedback sufficient to strongly stabilize H3K9me3 heterochromatin in post-mitotic cells by generating local enzyme concentrations capable of counteracting transient bursts of demethylation. This model does not require direct molecular interactions with adjacent nucleosomes and is favoured by a series of additional mechanisms including (i) the protection of chromatin-bound SUV39H1/2 from the turnovers of soluble proteins, which can explain the uncoupling between the cellular contents in SUV39H1 mRNA and protein; (ii) the cooperative dependence on the local density of the H3K9me3 of HP1α/β-dependent heterochomatin condensation and, dispensably (iii) restricted enzyme exchanges with chromocenters confining the reactive bursts of SUV39H1/2 in heterochromatin. This mechanism illustrates how seemingly static epigenetic states can be firmly maintained by dynamic and reversible modifications. © 2016 Elsevier B.V.
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms

hal-01467548
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467548
DOI : 10.1016/j.bbagrm.2016.11.006
PUBMED : 27876670

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Meiotic recombination predominantly occurs at discrete genomic loci called recombination hotspots, but the features defining these areas are still largely unknown (reviewed in refs 1-5). To allow a comprehensive analysis of hotspot-associated DNA and chromatin characteristics, we developed a direct molecular approach for mapping meiotic DNA double-strand breaks that initiate recombination. Here we present the genome-wide distribution of recombination initiation sites in the mouse genome. Hotspot centres are mapped with approximately 200-nucleotide precision, which allows analysis of the fine structural details of the preferred recombination sites. We determine that hotspots share a centrally distributed consensus motif, possess a nucleotide skew that changes polarity at the centres of hotspots and have an intrinsic preference to be occupied by a nucleosome. Furthermore, we find that the vast majority of recombination initiation sites in mouse males are associated with testis-specific trimethylation of lysine 4 on histone H3 that is distinct from histone H3 lysine 4 trimethylation marks associated with transcription. The recombination map presented here has been derived from a homogeneous mouse population with a defined genetic background and therefore lends itself to extensive future experimental exploration. We note that the mapping technique developed here does not depend on the availability of genetic markers and hence can be easily adapted to other species with complex genomes. Our findings uncover several fundamental features of mammalian recombination hotspots and underline the power of the new recombination map for future studies of genetic recombination, genome stability and evolution.
ISSN: 0028-0836

hal-00877681
https://hal.archives-ouvertes.fr/hal-00877681
DOI : 10.1038/nature09869
PUBMED : 21460839

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
Cancer is generally conceived as a dedifferentiation process in which quiescent post-mitotic differentiated cells acquire stem-like properties and the capacity to proliferate. This view holds for the initial stages of carcinogenesis but is more questionable for advanced stages when the cells can transdifferentiate into the contractile phenotype associated to migration and metastasis. Singularly from this perspective, the hallmark of the most aggressive cancers would correspond to a genuine differentiation status, even if it is different from the original one. This seeming paradox could help reconciling discrepancies in the literature about the pro-or anti-tumoral functions of candidate molecules involved in cancer and whose actual effects depend on the tumoral grade. These ambiguities which are likely to concern a myriad of molecules and pathways, are illustrated here with the selected examples of chromatin epigenetics and myocardin-related transcription factors, using the human MCF10A and MCF7 breast cancer cells. Self-renewing stem like cells are characterized by a loose chromatin with low levels of the H3K9 trimetylation, but high levels of this mark can also appear in cancer cells acquiring a contractile-type differentiation state associated to metastasis. Similarly, the myocardin-related transcription factor MRTF-A is involved in metastasis and epithelial-mesenchymal transition, whereas this factor is naturally enriched in the quiescent cells which are precisely the most resistant to cancer: cardiomyocytes. These seeming paradoxes reflect the bistable epigenetic landscape of cancer in which dedifferentiated self-renewing and differentiated migrating states are incompatible at the single cell level, though coexisting at the population level. © 2016-IOS Press and the authors. All rights reserved.
ISSN: 0888-6008

hal-01367146
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367146
DOI : 10.3233/BD-150210
PUBMED : 27177343

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Gastric cancer is one of the most common cancers in the world. The "economically developed countries" life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate. METHODOLOGY/PRINCIPAL FINDINGS: A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy. CONCLUSIONS/SIGNIFICANCE: Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments.
ISSN: 1932-6203

inserm-00871491
http://www.hal.inserm.fr/inserm-00871491
http://www.hal.inserm.fr/inserm-00871491/document
http://www.hal.inserm.fr/inserm-00871491/file/Milk_Fermented_by_Propionibacterium_freudenreichii.accepted.pdf
DOI : 10.1371/journal.pone.0031892

Éditeur(s) : HAL CCSD
Résumé : Food-grade dairy propionibacteria release beneficial short chain fatty acids (SCFAs), folic acid and cobalamin. They induce apoptosis via the mitochondrial death pathway. We investigated their synergy with drugs used in gastric and colorectal cancer.Fermented milk containing propionibacteria and SCFAS acetate and propionate, as well as its cell-free supernatant, induced apoptosis in gastric HGT-1 and colic HT-29. Characterization of cells revealed apoptosis induction evidenced by chromatin condensation, DNA laddering, emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet and cytochrome c release. Interestingly, the fermented milk was shown to potentiate the cytotoxic effect of molecules used in cancer chemotherapy, camptothecin and TRAIL (TNF Related Apoptosis Inducing Ligand).These results open new perspectives in the field of colon cancer cells prevention and/or treatment. Such a fermented product, or the propionibacterium alone, may be proposed as a food supplement to enhance the effects of anticancer treatments.
Les bactéries propioniques laitières produisent des acides gras volatils (AGV), acide folique et cobalamine, composés bénéfiques. Elles induisent l’apoptose via la voie mitochondriale. Nous avons recherché leur synergie avec des drogues utilisées dans le cancer gastrique ou colique.Un lait fermenté contenant des bactéries propioniques et les AGVs propionate et acétate a induit l’apoptose de cellules gastriques HGT-1 et coliques HT-29. L’étude des cellules a révélé l’induction de l’apoptose : condensation de la chromatine, fragmentation de l’ADN, l’émergence d’une population subG1, l’externalisation des phosphatidylserines et le relargage du cytochrome c. De manière intéressante, le lait fermenté a potentialisé les effets cytotoxiques de molécules utilisées en chimiothérapie, camptothécine et TRAIL (TNF Related Apoptosis Inducing Ligand).Ces résultats ouvrent de nouvelles perspectives dans le domaine du traitement ou de la prévention des cancers digestifs. Un tel produit fermenté, ou les propionibactéries seules, pourrait être proposé comme supplément alimentaire pour augmenter l’efficacité de traitements anti-cancéreux.
5. Colloque Intenational Molécules & Ingrédients Santé
Quimper, France

hal-01204307
https://hal.archives-ouvertes.fr/hal-01204307
PRODINRA : 261444

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Although many studies reported mechanisms involved in the positive regulation of estrogens (E2) target genes, very little is known concerning the repressive effect of E2. In this study, we explored the molecular mechanisms by which E2 regulates CXCR7 expression in breast cancer cells. Our results show that E2-mediated down-regulation of CXCR7 occurs at the transcriptional level as demonstrated using actinomycin D and requires estrogen receptor alpha (ERα). In addition, CXCR7 is a primary ERα-target gene because the effect of E2 does not require the synthesis of an intermediary protein as revealed by the translational inhibitor cycloheximide treatment. Using an inhibitor of the NFκB pathway and chromatin immunoprecipitation assays, we demonstrated that NFκB is necessary for the high expression of CXCR7 gene and is recruited to the proximal promoter of the CXCR7 gene. Interestingly, the chromatin immunoprecipitation analyses also showed that E2-treatment significantly prevented the recruitment of NFκB to the promoter. Altogether, our results demonstrate that E2, through ERα, directly down-regulates CXCR7 expression by interfering with NFκB transcription factor at the promoter level.
ISSN: 0006-291X

inserm-00808966
http://www.hal.inserm.fr/inserm-00808966
DOI : 10.1016/j.bbrc.2013.01.050
PUBMED : 23352615

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Homologous recombination is the key process that generates genetic diversity and drives evolution. SPO11 protein triggers recombination by introducing DNA double stranded breaks at discreet areas of the genome called recombination hotspots. The hotspot locations are largely determined by the DNA binding specificity of the PRDM9 protein in human, mice and most other mammals. In budding yeast Saccharomyces cerevisae, which lacks a Prdm9 gene, meiotic breaks are formed opportunistically in the regions of accessible chromatin, primarily at gene promoters. The genome-wide distribution of hotspots in this organism can be altered by tethering Spo11 protein to Gal4 recognition sequences in the strain expressing Spo11 attached to the DNA binding domain of the Gal4 transcription factor. To establish whether similar re-targeting of meiotic breaks can be achieved in PRDM9-containing organisms we have generated a Gal4BD-Spo11 mouse that expresses SPO11 protein joined to the DNA binding domain of yeast Gal4. RESULTS: We have mapped the genome-wide distribution of the recombination initiation sites in the Gal4BD-Spo11 mice. More than two hundred of the hotspots in these mice were novel and were likely defined by Gal4BD, as the Gal4 consensus motif was clustered around the centers in these hotspots. Surprisingly, meiotic DNA breaks in the Gal4BD-Spo11 mice were significantly depleted near the ends of chromosomes. The effect is particularly striking at the pseudoautosomal region of the X and Y chromosomes -- normally the hottest region in the genome. CONCLUSIONS: Our data suggest that specific, yet-unidentified factors influence the initiation of meiotic recombination at subtelomeric chromosomal regions.
ISSN: 1471-2164

inserm-00849779
http://www.hal.inserm.fr/inserm-00849779
http://www.hal.inserm.fr/inserm-00849779/document
http://www.hal.inserm.fr/inserm-00849779/file/1471-2164-14-493.pdf
DOI : 10.1186/1471-2164-14-493

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The cell-fate decision leading to gametogenesis is essential for sexual reproduction. In S. cerevisiae, only diploid MATa/α but not haploid MATa or MATα cells undergo gametogenesis, known as sporulation. We find that transcription of two long noncoding RNAs (lncRNAs) mediates mating-type control of sporulation. In MATa or MATα haploids, expression of IME1, the central inducer of gametogenesis, is inhibited in cis by transcription of the lncRNA IRT1, located in the IME1 promoter. IRT1 transcription recruits the Set2 histone methyltransferase and the Set3 histone deacetylase complex to establish repressive chromatin at the IME1 promoter. Inhibiting expression of IRT1 and an antisense transcript that antagonizes the expression of the meiotic regulator IME4 allows cells expressing the haploid mating type to sporulate with kinetics that are indistinguishable from that of MATa/α diploids. Conversely, expression of the two lncRNAs abolishes sporulation in MATa/α diploids. Thus, transcription of two lncRNAs governs mating-type control of gametogenesis in yeast.
ISSN: 0092-8674

hal-00877439
https://hal.archives-ouvertes.fr/hal-00877439
DOI : 10.1016/j.cell.2012.06.049
PUBMED : 22959267

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Thermal acclimation drastically alters thermotolerance of ectotherms, but the mechanisms determining this plastic response are not fully understood. The present study investigates the proteomic response (2D-DIGE) of adult Drosophila melanogaster acclimated at 11, 25 or 31 C. As expected 11 C-acclimation improved cold tolerance and 31 C-acclimation improved heat tolerance. We hypothesized that the marked organismal responses to acclimation could be detected at the proteomic level assuming that changes in the abundance of specific proteins are linked to the physiological changes underlying the phenotypic response. The 31 C-acclimated flies displayed a particular divergent proteomic profile where molecular chaperones made up a large number of the proteins that were modulated during heat acclimation. Many other proteins showed significant modulation during acclimation including proteins involved in iron ion and cell redox homeostasis, carbohydrate and energy metabolism, chromatin remodeling and translation, and contractile machinery. Interestingly the changes in protein abundance were often unrelated to transcriptional activity of the genes coding for the proteins, except for the most strongly expressed proteins (e.g. Hsp70). The 11 C-acclimation evoked weak proteomic response despite the marked effect on the organismal phenotype. Thus the acquired cold tolerance observed here may involve regulatory process such as posttranslational regulation rather than de novo protein synthesis.
ISSN: 0965-1748

hal-00826939
https://hal.archives-ouvertes.fr/hal-00826939
DOI : 10.1016/j.ibmb.2013.01.006
PUBMED : 23416132

Éditeur(s) : HAL CCSD Frontiers Media
Résumé : International audience
The yeast Candida glabrata has become the second cause of systemic candidemia in humans. However, relatively few genome-wide studies have been conducted in this organism and our knowledge of its transcriptional regulatory network is quite limited. In the present work, we combined genome-wide chromatin immunoprecipitation (ChIP-seq), transcriptome analyses, and DNA binding motif predictions to describe the regulatory interactions of the seven Yap (Yeast AP1) transcription factors of C. glabrata. We described a transcriptional network containing 255 regulatory interactions and 309 potential target genes. We predicted with high confidence the preferred DNA binding sites for 5 of the 7 CgYaps and showed a strong conservation of the Yap DNA binding properties between S. cerevisiae and C. glabrata. We provided reliable functional annotation for 3 of the 7 Yaps and identified for Yap1 and Yap5 a core regulon which is conserved in S. cerevisiae, C. glabrata, and C. albicans. We uncovered new roles for CgYap7 in the regulation of iron-sulfur cluster biogenesis, for CgYap1 in the regulation of heme biosynthesis and for CgYap5 in the repression of GRX4 in response to iron starvation. These transcription factors define an interconnected transcriptional network at the crossroads between redox homeostasis, oxygen consumption, and iron metabolism.
ISSN: 1664-302X

Droits : http://creativecommons.org/licenses/by/
hal-01323791
http://hal.upmc.fr/hal-01323791
http://hal.upmc.fr/hal-01323791/document
http://hal.upmc.fr/hal-01323791/file/fmicb-07-00645.pdf
DOI : 10.3389/fmicb.2016.00645

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Epigenetics is most often reduced to chromatin marking in the current literature, whereas this notion was initially defined in a more general context. This restricted view ignores that epigenetic memories are in fact more robustly ensured in living systems by steady-state mechanisms with permanent molecule renewal. This misconception is likely to result from misleading intuitions and insufficient dialogues between traditional and quantitative biologists. To demystify dynamic epigenetics, its most famous image, a Waddington landscape and its attractors, are explicitly drawn. The simple example provided, is sufficient to highlight the main requirements and characteristics of dynamic gene networks, underlying cellular differentiation, de-differentiation and trans-differentiation.
ISSN: 0248-4900

inserm-00920766
http://www.hal.inserm.fr/inserm-00920766
http://www.hal.inserm.fr/inserm-00920766/document
http://www.hal.inserm.fr/inserm-00920766/file/Dynamic_Epigenetics.pdf
PUBMED : 24111561